OBJECTIVES: As more effective interventions for treating Cytomegalovirus retinitis (CMVR) through various routes—intravenous (IV), oral (OR), intravitreal injection (IVT) and intraocular implant (IMP) have become available and there are large variations in clinical practice in Thailand, this study is to evaluate the incremental cost-effectiveness ratio (ICER) of providing 1) IVT; 2) IV/OR; and 3) IMP to the HIV/AIDS patients presenting with CMVR. METHODS: This was a simulation study for which the input parameters were derived from systematic review of literature, hospital-based survey, and patient interviews.  The analysis assumed a Thai health care system.  However, the model was run using both societal and health care provider’s perspectives. RESULTS: IVT was the cheapest and a cost-effective option for treating CMVR patients with or without antiretroviral treatment (ART).  If  ART is available, moving from IVT to IV/OR was also likely to be a cost-effective option in a Thai setting.  With the current evidence, offering IMP was not likely to be cost-effective. Providing treatments for patients with bilateral CMVR was more cost-effective than those with unilateral CMVR, and offering treatments for the patients with antiretroviral drugs was better value for money than treating patients without ART. CONCLUSIONS: Our models suggest that IV/OR should be recommended for treatment of unilateral and bilateral CMVR in the Thai health care system.